This program is a continuation of our studies to develop and evaluate appropriate animal models to study biological principles that may be useful in understanding prostatic cancer. Emphasis has been placed on defining and characterizing seven transplantable rat tumor sublines from the Dunning R-3327 tumor line that will cover the spectrum of: slow to fast growth rates; well differentiated to anaplastic; androgen dependent to sensitive to insensitive; and high metastatic frequency to low and different organ sites for distant metastatic lesions. The development and careful characterization of these different models is required to correspond to the broad spectrum of human porstate cancers that are seen clinically (androgen sensitive, insensitive, states of differentiation, etc.). Our past studies on these models have revealed an enzymatic index that allows one to predict androgen respose from a smal biopsy sample by biochemical method. These approaches are now being applied by others to human samples. Tumor cell heterogeneity has been established in these models and studies reveal this is an important mechanism in the relapse to hormonal and possibly non-hormonal control. The mechanism in the tumors leading to genetic instability, heterogeneity, clone selection and tumor progression will be studied with emphasis on the changes in morphological patterns and specific structural elements that may be associated with these progressions. A series of valuable models with wide ranges in metatstatic potential have been developed and these will be used to test some of the current thinking on mechanism and biological principles of metastasis. This will be a preliminary study to provide an overview of the potential merits of these models for studies of prostate metastasis. These models will be tested using the already completed and published protocols used in the National Cooperative Chemotherapeutic Trials of the National Prostatic Cancer Project to determine which of the seven tumors respond most closely to what has been observed in humans. Chemotherapy against the more rapidly growing tumors will be compared to the slower growing tumors.